The asymmetric dihydroxylation of olefins with osmium tetroxide to yield optically active glycols has been described extensively in the literature (Sharpless, K. B., et al. J. Org. Chem. 1992, 56, 4585 and references cited therein). In a dihydroxylation reaction, an olefinic substrate is transformed into a dihydroxyl-substituted compound (i.e., a glycol) through the addition of two hydroxyl groups across the double bond. During an asymmetric dihydroxylation reaction, the hydroxyl groups are added stereoselectively across a particular face of the prochiral olefin double bond. This stereofacial selectivity is made possible by chiral mediators, in particular, a chiral tertiary amine ligand that forms a complex with osmium tetroxide (Hentges, S. G., et al. J. Am. Chem. Soc. 1980, 102, 4263; and Jacobsen, E. N., et al. Ibid. 1988, 110, 1968).
The optically active glycols produced by this asymmetric reaction are important chiral starting materials for organic synthesis. For instance, these glycols can be used advantageously as precursors of more complex molecules. In particular, pharmacologically active compounds, such as the anticancer drug taxol which can be prepared from optically active 2,3-dihydroxy-3-phenylpropionates (Denis, J. -N., et al. J. Org. Chem. 1990, 55, 1957). Also, optically pure 2,3-dihydroxy-3-arylpropionates prepared from cinnamate esters have been used to produce antihypertensive drugs such as Diltiazem (PCT AU88/00345). Also, optically pure stilbene diol (hydrobenzoin) from stilbene has been used as chiral ligand for Lewis-acid catalyzed asymmetric Diels-Alder reactions (Devine, P. N. and Oh, T., J. Org. Chem. 1992, 57, 396). Furthermore, optically pure glycols can be used to prepare chemically distinguishable or separable diastereomeric mixtures from racemic carbonyl-containing compounds; i.e., ketals and acetals from ketones and aldehydes, respectively (Mukaiyama, T., et al; Synthesis, 1987, 1043).
lnitially, asymmetric dihydroxylation reactions were carried out using stoichiometric amounts of osmium tetroxide-chiral ligand complexes (Hentges, S. G. et al. J. Am. Chem. Soc. 1980, 102, 4263; Yamada, T. et al. Chem. Lett. 1986, 131; Tomioka, K., et al. J. Am. Chem. Soc. 1987, 109, 6213). More recently, however, the utility of this reaction has been extended by the development of catalytic processes in which less than a stoichiometric amount of precious osmium tetroxide-chiral ligand complex is employed. This catalytic process is made possible by using a stoichiometric amount of a secondary oxidant which is effective to reoxidize or regenerate the osmium tetroxide from the lower valent osmium species produced during the dihydroxylation reaction (Sharpless, K. B. et al. J. Am. Chem. Soc. 1989, 111, 1123; Sharpless, K. B. et al. Tetrahedron Lett. 1990, 31, 2999). Generally, high degrees of conversion are observed using a slight molar excess of the secondary oxidant relative to the initial amount of olefin present in the reaction mixture.
U.S. Pat. No. 4,217,291 discloses a method for the chemical reoxidation of osmium species in a valence state less than 5 to a valence state greater than 5. The chemical oxidant is an organic secondary or tertiary hydroperoxide. This reference also discloses the dihydroxylation of olefins to glycols using hydroperoxide in the presence of catalytic amounts of osmium tetroxide.
However, the commercial success of a particular synthetic process hinges, more often than not, on the costs associated with that process versus a competing process. Although the asymmetric dihydroxylation of olefins proceeds relatively well using a catalytic amount of osmium tetroxide and chiral ligand plus a stoichiometric amount of secondary oxidant, such as N-methylmorpholine-N-oxide or potassium ferricyanide, the cost of the secondary oxidant is not insignificant especially in the large-scale manufacturing of fine chemicals. Moreover, other factors are equally important in deliberations to lower the number and corresponding amounts of reagents used in manufacturing methods. Such additional considerations include waste disposal and environmental factors, workplace and health regulations, as well as productivity and efficiency issues.
Thus, there exists a need to improve existing processes to meet the demands of the marketplace, the needs of the community and to satisfy or even preempt requirements imposed by regulatory agencies.